PMID- 8943383
OWN - NLM
STAT- MEDLINE
DCOM- 19961227
LR  - 20181130
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 157
IP  - 11
DP  - 1996 Dec 1
TI  - Allospecific CD8+ Tc1 and Tc2 populations in graft-versus-leukemia effect and 
      graft-versus-host disease.
PG  - 4811-21
AB  - Allogeneic CD8+ T cells mediate both a graft-vs-leukemia (GVL) effect and 
      graft-vs-host disease (GVHD). To evaluate whether CD8 cells of defined cytokine 
      phenotype differentially mediate these processes, alloreactive donor CD8+ T cells 
      preferentially secreting type I or type II cytokines were generated by 
      alloantigenic priming in vitro in the presence of IL-12 or IL-4, respectively. 
      Both cytokine-secreting subsets lysed allogeneic tumor targets in vitro ("Tc1" 
      and "Tc2" subsets). A transplantation model was established (B6 into B6C3F1, 1050 
      cGy host irradiation) using the 32Dp210 myeloid line (bcr/abl transfected, H-2k; 
      1 x 10(4) tumor cells/recipient). Compared with leukemia controls (death at 12.9 
      days post-bone marrow transplantation), both Tc1 and Tc2 recipients were 
      conferred a survival advantage. At cell doses of 2 to 2.5 x 10(7), the 
      Tc1-mediated GVL effect (mean survival of 34.2 days) was more potent than the 
      Tc2-mediated GVL effect (mean survival of 20.5 days; Tc1 > Tc2, p = 0.009). On 
      day 15, histologic examination showed that Tc1 recipients had undetectable tumor 
      burdens, whereas Tc2 recipients had extensive leukemic infiltrates. However, Tc2 
      recipients had essentially no histologic evidence of GVHD, whereas Tc1 recipients 
      had mild to moderate GVHD (average GVHD scores of 1/40 and 9.3/40, respectively). 
      In contrast, recipients of uncultured CD8+ donor T cells developed severe GVHD 
      (average GVHD score of 26.7/40). Because in vitro-generated, alloreactive Tc1 and 
      Tc2 populations mediated GVL with reduced GVHD, we conclude that both subsets may 
      improve the therapeutic outcome of allogeneic T cell transfers in patients with 
      leukemia.
FAU - Fowler, D H
AU  - Fowler DH
AD  - Transplantation Therapy Section, Medical Oncology Branch, National Cancer 
      Institute, National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Breglio, J
AU  - Breglio J
FAU - Nagel, G
AU  - Nagel G
FAU - Eckhaus, M A
AU  - Eckhaus MA
FAU - Gress, R E
AU  - Gress RE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Cytokines)
RN  - 0 (FASLG protein, human)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Fasl protein, mouse)
RN  - 0 (Ligands)
RN  - 0 (Membrane Glycoproteins)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Animals
MH  - Bone Marrow Transplantation/immunology/pathology
MH  - CD8-Positive T-Lymphocytes/*classification/drug effects/*immunology
MH  - Cytokines/metabolism
MH  - Cytotoxicity, Immunologic
MH  - Fas Ligand Protein
MH  - Graft Survival/immunology
MH  - Graft vs Host Disease/etiology/*immunology/pathology
MH  - Graft vs Host Reaction/*immunology
MH  - Humans
MH  - In Vitro Techniques
MH  - Intestines/immunology/pathology
MH  - Leukemia, Experimental/*immunology/pathology/*therapy
MH  - Ligands
MH  - Liver/immunology/pathology
MH  - Membrane Glycoproteins/immunology
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Mice, Inbred C57BL
MH  - Neoplasm Transplantation
MH  - T-Lymphocyte Subsets/*immunology
MH  - Transplantation, Homologous
EDAT- 1996/12/01 00:00
MHDA- 1996/12/01 00:01
CRDT- 1996/12/01 00:00
PHST- 1996/12/01 00:00 [pubmed]
PHST- 1996/12/01 00:01 [medline]
PHST- 1996/12/01 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1996 Dec 1;157(11):4811-21.